Avascular Necrosis and Glucocorticoid Use

AVASCULAR NECROSIS and GLUCOCORTICOID USE
(Prednisone and similar) Edited from a Dec. 2004 article

Last update 20 July 2010

AVN is bone death due to lack of blood supply)

It represents an inability to supply adequate blood oxygen to underlying bone.

AVN is extremely rare in healthy individuals.
There are numerous causes for AVN other than prednisone usage.

Preferred Examination

MRI is the most sensitive means of diagnosing AVN. MRI provides the criterion standard of noninvasive diagnostic evaluation. It is more sensitive than CT scanning or planar scintigraphy, and is much more sensitive than plain film radiography for detecting AVN.

The femoral head is the most vulnerable site for development of AVN.

The site of necrosis is usually immediately below the weight bearing articular surface of the bone, the anterolateral aspect of the femoral head.
This is the site of greatest mechanical stress.
AVN only occurs in fatty marrow, which contains a sparse vascular supply.

In contrast, hematopoietic bone marrow has a rich blood supply.

Elderly persons are at decreased risk for developing AVN.

Fat cells become smaller in this age group.

The space between fat cells fills with a loose reticulum and mucoid fluid, which are resistant to AVN.
This is termed gelatinous marrow and, even in the presence of increased intramedullary pressure, intersitial fluid is able to escape into the blood vessels leaving the spaces free to absorb additional fluid.

Non-traumatic AVN is commonly bilateral and occurs in a younger population.
Non-traumatic bilateral AVN usually occurs at different times and progresses at different rates in each individual hip.

Clinical Details

AVN demonstrates no distinguishing clinical features during examinations.
Patients do not experience pain during the ischemic episode (initial lack of blood flow)..
Occult (hidden) AVN can be present for more than 5 years before the onset of symptoms.
Patients may be asymptomatic or may develop pain gradually and insidiously

Patients can experience a decreased range of motion (ROM), and walk with a limp.
Pain can be excruciating and of sudden onset, with the patient able to note the exact time and date it began.
Radiographic findings may appear after a delay of several months to years following the onset of symptoms.

Incidence of AVN is increasing.

The causes include greater use of exogenous steroids and an increase in trauma.
In the U.S. incidence is approximately 15,000 cases per year.
The incidence is increased because of a greater use of exogenous steroids, an increase in trauma, and alcohol abuse.

The relative frequencies of the most common causes of AVN are associated with

Alcoholism (20-40%) and
steroid treatment (35-40%)
Idiopathic (causes unknown) (20-40%).

Mortality/Morbidity

Severe joint destruction resulting from deterioration and leading to a major surgical procedure occurs within 3 years following diagnosis in 50% of patients.
Femoral head collapse usually occurs within 2 years after development of hip pain.

Internationally

Sickle Cell Disease (SCD) and the hemoglobinopathies are the major cause of AVN in African countries such as the Democratic Republic of the Congo (formerly Zaire).
Thalassemia is prevalent in southern Mediterranean Europeans and people from Southeast Asia.
Legg-Calvé-Perthes (LCP) disease is the most common cause of AVN in children.

The time of onset ranges from age 3-10 years, with the highest incidence occurring from age 6-8 years.
The greatest incidence is in Japanese, Mongolian, Eskimo, and Central European children, with a low incidence in blacks and American Indians.

LCP disease affects males 4 times more frequently than it affects females.

Racial Background

Predisposing conditions, such as SCD, are concentrated in the African American population.
Beta thalassemia is common in Southern Europeans and Southeast Asians.

Age

AVN usually occurs in patients in the third-to-fifth decades unless predisposing conditions exist that place different age groups at risk.

Some researchers think that the cause of AVN most likely is related to thrombosis or embolization of smaller arteries of the femoral head by lipid droplets, abnormal red blood cells (as in SCD), or nitrogen bubbles from Caisson disease.

Other researchers think that vasculopathy with structural damage to the arterial or venous walls from vasculitis, radiation necrosis, or release of vasoactive substances (as in Gaucher disease) is the cause.
Still other researchers think that increased intraosseous pressure from enlargement of intramedullary fat cells or osteocytes is a factor.
The consensus indicates that the cause is multifactorial and that it is better to deal with the disease as the end result of a number of different factors with the final common pathway resulting in bone death and collapse of the femoral head.

Six possible mechanisms may be present.

Occlusion of small vessels occurs related to fat emboli from the liver.
Increased intraosseous (internal to bone) pressure results from a steroid-related increase in the size of the intramedullary fat cells without an equivalent compensatory loss of trabecular and cortical bone.
Fat emboli become hydrolyzed to free fatty acids, which are toxic to vascular endothelium, causing intravascular coagulation.
Angiogenesis is inhibited by a reduction of proteolytic activity by the synthesis of polyclonal antithyroid hormone receptor alpha-1 antibody (PA).
A direct toxic effect occurs on osteogenic (bone generating) cells
Steroid use causes conversion of hematopoietic marrow to fatty marrow, a prerequisite for the development of AVN.

The conversion may be related to steroid-induced reduced blood flow.

Steroid caused AVN exposure threshold is approximately 2000 mg of prednisone administered continuously.

However, AVN has been described following lower doses.
The risk of AVN is greater risk in patients treated for a short duration (6 wk) with high doses (>20 mg).

The risk of AVN in low-dose steroid therapy is controversial.

Studies both link such therapy to the disease and also refute the role of such treatment.
High doses of steroids administered within a relatively short period are more of a causative factor than cumulative dose or duration of therapy.

AVN can occur up to 3 years following cessation of steroid therapy.

Steroid-induced AVN is more severe than AVN caused by other conditions.

Underlying demineralization and accelerated osteolysis place the weight-bearing surface of the femoral head at increased risk of collapse.

Late complications

Continued weigh tbearing results in flattening of the articular cartilage.
Capillary invasion results in articular cartilage resorption.
Such a loss predisposes patients to ostearthritis

Individuals with systemic lupus erythematosus (SLE) and renal allograft recipients treated with steroids have the highest incidence of AVN.

Autoimmune vasculitides may present similar susceptibility.

In renal transplantation, a high association exists between AVN and prednisone doses greater than 100 mg/d within the first month following transplantation.
AVN is uncommon in transplant recipients taking less than 100 mg/d.
Risk is increased of underlying bone changes associated with chronic renal disease, such as hypophosphatemia.
Reducing renal bone disease with better dialysis (increasing ionized calcium in the dialysate) and medical management significantly reduces the incidence of AVN.

A delay in diagnosis may occur because of pain reduction provided by concurrent administration of steroids.
In systemic lupus erythematosus, AVN is the dominant orthopedic problem in patients with SLE.

Patients with SLE with vasculitis and Raynaud syndrome are at higher risk for developing AVN.Patients usually are younger and have more active disease with multiple organ involvement.

Generally, hip replacement is the only treatment with a positive outcome.

Bond decompression accomplished by drilling into the bone to allow blood to reach the area may postpone hip replacement.
If necrosis isn't severe, a surgical replacement of the disease bone may be successful.

If AVN is in the early stages, free vascularized fibular grafting (FVFG) can be done. In the FVFG process, blood rich bone harvested from the patient is grafted into the damaged area. If successful, this can postpone hip replacement. This is approved for use in the U.K., but yet experimental in the U.S.A.

(Above extracted and edited from http://www.emedicine.com/RADIO/topic70.htm)